Pharmacokinetics III: Drug Interactions & Individual Variation to Drug Responses

Question 1

What are Drug Interactions?

Answer 1

A change in the magnitude or duration of response of one drug due to presence of a second drug

Question 2

Are drug interactions chemical or physiological interactions?

Answer 2

Physiological

Question 3

What is a rare example of a chemical interaction between two drugs?

Answer 3

Thiopental + Suxamethonium = Precipitate

Question 4

What are the TWO potentially dangerous effects of drug interactions?

Answer 4

1. Additive - Drug B BOOSTS Drug A effects
2. Negating Effect - Drug B DECREASES Drug A effect

Question 5

What is the equation for the Therapeutic Index for a drug?

Answer 5

Question 6

What are the some pharmacodynamic considerations for drugs with NARROW therapeutic ranges?

Answer 6

• Small REDUCTION in drug plasma -> Loss of efficacy
• Small INCREASE in drug plasma -> Toxicity

Question 7

What is a pharmacokinetic consideration if the concentration-response for a drug is STEEP?

Answer 7

Small change in drug plasma -> Big change in effect

Question 8

Where do Pharmacodynamic Drug Interactions occur?

Answer 8

At the receptor

Question 9

How is gastrointestinal absorption affected by drugs that inhibit gastric emptying?

Answer 9

Slowed absorption

Question 10

How is gastrointestinal absorption affected by drugs that speed up gastric emptying?

Answer 10

Accelerated absorption

Question 11

Which drug do Ca2+ and Fe2+ form insoluble complexes with in the GI tract?

Answer 11

Tetracycline

Question 12

Which TWO drugs does Colestyramine (bile acid-binding resin) bind in the GI tract?

Answer 12

Warfarin and Digoxin

Question 13

What effect does complex formation in the GI tract cause?

Answer 13

• DECREASED drug absorbance
• DECREASED drug plasma concentrations

Question 14

What happens to the levels of free drugs in the plasma with concurrent administration of two drugs with high binding to plasma proteins?

Answer 14

INCREASED free drug levels for both drugs

Question 15

What is Enzyme Induction?

Answer 15

Increase in enzyme activity caused by a foreign compound (inducer)

Question 16

Does Enzyme Induction occur slowly or fast?

Answer 16

Slowly

Question 17

TRUE OR FALSE:
Enzyme Induction requires a single exposure to the inducer?

Answer 17

False.
Requires repeated / prolonged exposure

Question 18

What are the THREE roles of Enzyme Induction in drug interactions?

Answer 18

1. Accelerates clearance
2. Reduces drug action
3. Increases formation of toxic metabolites

Question 19

What inducer enhances the metabolism of Barbiturates, Estradiol, Phenytoin, and Quinine?

Answer 19

Barbiturates

Question 20

What inducer enhances the metabolism of Dexamethasone, Digitoxin, and Theophylline?

Answer 20

Phenytoin

Question 21

What inducer enhances the metabolism of Anticoagulants, and Oral Contraceptives?

Answer 21

Rifampicin

Question 22

What is Enzyme Inhibition?

Answer 22

Decreased enzyme activity caused by a foreign compound

Question 23

Does Enzyme Inhibitions occur slowly or fast?

Answer 23

Fast

Question 24

What are the THREE roles of Enzyme Inhibition in drug interactions?

Answer 24

1. Requires on a single dose
2. Impairs drug clearance
3. Prolongs drug action

Question 25

What inhibitor inhibits the metabolism of Diazepam and Warfarin?

Answer 25

Cimetidine

Question 26

What inhibitor inhibits the metabolism of Antipyrine, Ethanol, Phenytoin, and Warfarin?

Answer 26

Disulfiram

Question 27

What inhibitor inhibits the metabolism of Methanol?

Answer 27

Ethanol

Question 28

How does Hepatic blood flow affect the rate of drug metabolism?

Answer 28

Reduced hepatic blood flow = Reduced metabolism

Question 29

Which types of drugs are particularly susceptible to changes in hepatic blood flow?

Answer 29

First-Pass metabolism drugs

Question 30

What are the THREE main mechanisms of renal excretion?

Answer 30

1. DECREASED protein binding would INCREASE filtration and elimination 2. Inhibition of tubular secretion 3. Alter urine flow and/or urine pH